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. 2014 Dec 14;20(46):17516-24.
doi: 10.3748/wjg.v20.i46.17516.

Cytokine production in patients with cirrhosis and TLR4 polymorphisms

Juan Camilo Nieto  1 , Elisabet Sánchez  1 , Eva Román  1 , Silvia Vidal  1 , Laia Oliva  1 , Carlos Guarner-Argente  1 , Maria Poca  1 , Xavier Torras  1 , Cándido Juárez  1 , Carlos Guarner  1 , German Soriano  1
Affiliations

Cytokine production in patients with cirrhosis and TLR4 polymorphisms

Juan Camilo Nieto et al. World J Gastroenterol. .

Abstract

Aim: To analyze the cytokine production by peripheral blood cells from cirrhotic patients with and without TLR4 D299G and/or T399I polymorphisms.

Methods: The study included nine patients with cirrhosis and TLR4 D299G and/or T399I polymorphisms, and 10 wild-type patients matched for age, sex and degree of liver failure. TLR4 polymorphisms were determined by sequence-based genotyping. Cytokine production by peripheral blood cells was assessed spontaneously and also after lipopolysaccharide (LPS) and lipoteichoic acid (LTA) stimulation.

Results: Patients with TLR4 polymorphisms had a higher incidence of previous hepatic encephalopathy than wild-type patients (78% vs 20%, P = 0.02). Spontaneous production of interleukin (IL)-6 and IL-10 was lower in patients with TLR4 polymorphisms than in wild-type patients [IL-6: 888.7 (172.0-2119.3) pg/mL vs 5540.4 (1159.2-26053.9) pg/mL, P < 0.001; IL-10: 28.7 (6.5-177.1) pg/mL vs 117.8 (6.5-318.1) pg/mL, P = 0.02]. However, the production of tumor necrosis factor-α, IL-6 and IL-10 after LPS and LTA stimulation was similar in the two groups.

Conclusion: TLR4 polymorphisms were associated with a distinctive pattern of cytokine production in cirrhotic patients, suggesting that they play a role in the development of cirrhosis complications.

Keywords: Genetic factors; Hepatic encephalopathy; Infections; Inflammatory response.

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Figures

Figure 1
Figure 1
Cytokine production in patients with cirrhosis and TLR4 polymorphisms and wild-type patients. A: TNF-α concentration in supernatants of unstimulated and LPS and LTA stimulated peripheral blood cells; B: IL-6 concentration in supernatants of unstimulated and LPS and LTA stimulated peripheral blood cells; and C: IL-10 concentration in supernatants of unstimulated and LPS and LTA stimulated peripheral blood cells. TNF-α: Tumour necrosis factor-alpha; LPS: Lipopolysaccharide; LTA: Lipoteichoic acid; IL: Interleukin.
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